Plasmapheresis filtration module having improved sealing means

ABSTRACT

A plasmapheresis filtration module having stacked grooved plates interleaved with membranes, enclosed in a unitary, flexible, impermeable envelope, sealing being effected by pressing the membranes between blood flow channels and a sealing surface on a plasma side support.

FIELD OF THE INVENTION

This invention relates to plasmapheresis by filtration and, moreparticularly, to apparatus for plasmapheresis by membrane filtration.

BACKGROUND INFORMATION

Plasmapheresis is a process of separating plasma from whole blood. Theplasma-depleted blood is comprised principally of cellular components,e.g., red blood cells, white blood cells and platelets. Plasma iscomprised largely of water, but also contains proteins and various othernoncellular compounds, both organic and inorganic.

Continuous plasmapheresis is the process of continuously removing wholeblood from a subject, separating plasma from the blood and returning theplasma-depleted blood to the subject in a continuous extracorporealcircuit.

Plasmapheresis is currently used to obtain plasma for varioustransfusion needs, e.g., preparation of fresh-frozen plasma, forsubsequent fractionation to obtain specific proteins such as serumalbumin, to produce cell culture media, and for disease therapiesinvolving either the replacement of plasma or removal of specificdisease-contributing factors from the plasma.

Plasmapheresis can be carried out by centrifugation or by filtration.Generally, in known filtration apparatus, whole blood is conducted in alaminar flow path across one surface, i.e., the blood side surface, of amicroporous membrane with a positive transmembrane pressure difference.Useful microporous membranes have pores which substantially retain thecellular components of blood but allow plasma to pass through. Suchpores are referred to herein as cell-retaining pores. Typically,cell-retaining pore diameters are 0.1 μm to 1.0 μm.

Various filtration devices for plasmapheresis are disclosed in theliterature. U.S. Pat. No. 3,705,100 discloses a center-fed circularmembrane having a spiral flow path. U.S. Pat. No. 4,212,742 discloses adevice having divergent flow channels. German Pat. No. 2,925,143discloses a filtration apparatus having parallel blood flow paths on oneside of a membrane and parallel plasma flow paths, which areperpendicular to the blood flow paths, on the opposite surface of themembrane. U.K. Patent Application 2,037,614 discloses a rectilineardouble-membrane envelope in which the membranes are sealed together atthe ends of the blood flow path. U.K. Patent Specification 1,555,389discloses a circular, center-fed, double-membrane envelope in which themembranes are sealed around their peripheries. German Pat. No. 2,653,875discloses a circular, center-fed double-membrane device in which bloodflows through slot-shaped filter chambers.

It is an object of this invention to provide a plasmapheresis filtrationmodule which, if desired, can be used for plasmapheresis byreciprocatory pulsatile filtration. It is a further object to providesuch a module which is easy-to-assemble and sterilizable andcharacterized by rigid flow paths and sealing of membranes withoutgaskets or adhesives.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an exploded view of the preferred module of the invention.

FIG. 2 is a plan view of a blood side support of the module of FIG. 1.

FIG. 3 is a plan view of a plasma side support of the module of FIG. 1.

FIG. 4 is a cross-sectional view of a central sealing region in themodule of FIG. 1.

FIG. 5 is an elevational view in cross-section of the attachment of aninlet or outlet tube to the module of FIG. 1.

FIG. 6 is a cross-sectional view of a module of the invention pressedbetween clamp jaws.

FIG. 7 is an elevational view in cross-section of reciprocating plungersused with the module of FIG. 1.

FIG. 8 is a perspective view of an alternative blood side support whichmay be used in the invention.

FIG. 9 is a perspective view of a plasma side support which can be usedwith the blood side suport of FIG. 8.

FIG. 10 is a perspective view of a second illustrative embodiment of amodule of the invention comprising the supports of FIGS. 8 and 9.

DISCLOSURE OF THE INVENTION

For further comprehension of the invention and of the objects andadvantages thereof, reference may be had to the following descriptionand to the appended claims in which the various novel features of theinvention are more particularly set forth.

The invention resides in a plasmapheresis filtration module comprising aplanar membrane pressed between a plasma side support having an inletsealing surface and a blood side support having narrow blood flowchannels opposite the sealing surface. The narrow channels pressedagainst the inlet sealing surface provide a seal which prevents bloodfrom entering the plasma side of the membrane as further describedbelow.

In a preferred embodiment, the membrane is circular and has a centralinlet with a generally radial blood flow path extending therefrombetween the blood side support and the membrane.

The invention further resides in such a preferred module in which one ormore of the following advantageous features are employed: generallyradial plasma flow channels extending from an inlet sealing surface to aplasma collection channel and blood flow channels which extend radiallyfrom the inlet to a plasma-depleted blood collection channel; plasma andblood flow channels which are offset; plasma flow channels which extendin zones of progressively greater numbers; entrances to the blood flowchannels which uniformly decrease in depth from greater than about 15mils (0.4 mm), preferably about 15 to 20 mils (0.4 to 0.5 mm), to about4 to 15 mils (0.1 to 0.4 mm), preferably about 4 to 10 mils (0.1 to 0.3mm), each of which has an initial width of about 4 to 20 mils (0.1 to0.5 mm) and each of which preferably has a cross-sectional area whichremains substantially constant as the channels decrease in depth; and, aperimeter border of short narrow channels on the blood side support anda peripheral sealing surface on the plasma side support, or a series ofplasma-depleted blood collection channels on the blood side support.

In the description and examples of the invention which follow, the term"forward" is used to indicate a direction generally away from the sourceof blood; "reverse" indicates a direction generally towards the sourceof blood. Transmembrane pressure difference is determined by subtractingthe pressure on the plasma side, i.e., the second surface of themembrane, from the pressure on the blood side, i.e., the first surfaceof the membrane. "Cell-retaining pores" means pores which substantiallyretain cellular components but allow plasma to pass through themembrane.

Plasmapheresis by filtration is enhanced by the use of fouling-reducingtechniques, e.g., pulsatile flow, reciprocatory pulsatile flow and highblood flow rate via recirculation. Plasmapheresis using reciprocatorypulsatile flow, which is the invention of one other than the inventorherein, comprises the steps of:

(1) conducting blood in a forward direction over a first surface, i.e.,a blood side surface, of each of one or more membranes havingcell-retaining pores;

(2) terminating the forward conducting of blood over the first surfaceof each membrane;

(3) conducting the blood in the reverse direction over said firstsurface, the volume of blood flowed in the reverse direction being lessthan the volume of blood flowed in the forward direction in step (1);

(4) repeating steps (1)-(3) in sequence and collecting plasma whichpasses through each membrane from a second surface, i.e., a plasma sidesurface, thereof and collecting plasma-depleted blood from said firstsurface.

Other steps may also be included, e.g., recycling the plasma-depletedblood, treating plasma during filtration, diluting the blood with acompatible fluid and measuring various biologically significant factors.

From the location at which the blood first contacts the membrane, whichmay or may not be near a point on an edge or end of the membrane, bloodis conducted in a forward direction in one or more flow paths. A flowpath is the space through which the blood flows on the first surface ofthe membrane. Typically the depth of blood in each flow path is lessthan about 30 mils (0.76 mm).

Plasma is driven through the cell-retaining pores in the membrane by apositive transmembrane pressure difference. Typically, positivetransmembrane pressure difference is generated primarily by resistanceto forward blood flow, but it can also be generated in other ways, e.g.,by decreasing pressure on the plasma on the second surface.

The amount of transmembrane pressure difference that can be withstood byblood without hemolysis is largely a function of cell-retaining poresize which is, typically, 0.1 to 1.0 μm, diameter. For most purposes,the preferred pore diameter is about 0.4 to 0.6 μm. In this range, apositive transmembrane pressure difference of no more than about 4 psi(28 kPA) is desirable. When the pore diameter is smaller or larger,higher or lower transmembrane pressure differences, respectively, areacceptable, although it is preferred that the transmembrane pressuredifference be kept low, e.g., below about 1.5 psi (10 kPa).

After the forward conducting of blood, the blood is conducted in thereverse direction in each flow path. The frequency and volume of thereciprocatory pulses are selected to maximize the flow of plasma throughthe membrane without causing extensive blood trauma. In a blood flowpath having a height of about 4 to 10 mils (102 to 254 μm), a usefulfrequency and volume are about 20 to 140 pulsations per minute and 0.5to 4 mL per pulsation, preferably about 3 mL. Said parameters should beselected to provide a mean linear velocity up to about 400 mm-sec⁻¹,preferably, up to about 250 mm-sec⁻¹. The net volume of blood flowed inthe reverse direction is less than the net volume of blood flowedforward.

The blood which approaches the ends of each flow path is plasma-depletedblood. It is collected and conducted away from the module by anysuitable means, as is the plasma which flows through the membrane.

Any type of useful planar membrane(s) in any suitable shape,configuration or arrangement can be used. Similarly, any suitable meanscan be used to conduct blood to the membrane and plasma-depleted bloodand plasma from the membrane.

Referring now to the drawings, which are illustrative only, FIGS. 1 to 7illustrate modules having an end plate which has reciprocatory pulsecavities integral therewith and which is the invention of anotherinventive entity. Referring to FIG. 1, which illustrates a partiallyexploded view of the module, the module comprises a clampable stack ofplates 19A, 19B, 32, between which, suitable membranes, not shown, areinterleaved. The plates are flexible and require external structuralsupport, such as is described below with reference to FIGS. 5 and 6, toeffect sealing and to compensate for compliance and tolerance within themodule. Blood is conducted into the module via module inlet 20 in endplate 19B and is conducted through matched ports in plates 32, 19A. Endplate 19A is about 0.19 inch (4.8 mm) thick; end plate 19B and plate 32are about 0.08 inch (2.0 mm) thick; the module is about 8 inches (0.2 m)in diameter.

From module inlet 20 in end plate 19A, the blood is conducted throughshallow channel 21, 0.2 inch (5.1 mm) wide×0.06 inch (1.5 mm) deep, intoinlet reciprocatory pulse cavity 22 which has a volume of about 3 mL andis about 2 inches (50.8 mm) in diameter×0.06 inch (1.5 mm) deep. Cavity22 is employed in the generation of reciprocatory pulsations asdescribed below. From cavity 22, the blood is conducted through shallowchannel 23, 0.5 inch (127 mm) wide×0.13 inch (3.3 mm) deep, to bloodflow path inlet 24 which is about 0.38 inch (9.7 mm) in diameter, i.e.,cavity 22 is between module inlet 20 and blood flow path inlet 24. Theblood is conducted through port 24, and through a matched port in plate32 and in the membranes, to blood flow paths lying between each membraneand one surface of a plate; e.g., on a membrane lying beween end plate19A and adjacent plate 32, the blood flow path is between the membraneand the interior surface of end plate 19A, which is a blood sidesupport, as illustrated for plate 32 in FIG. 2. The blood in the bloodflow paths is conducted radially to plasma-depleted blood collectionchannels and from there, through matched flow path outlets 25 andthrough branch channels 26 to outlet reciprocatory pulse cavity 27 inend plate 19A. The branch channels from the four outlets 25, which areequidistant from each other, begin as four channels each about 0.250inch (6.4 mm) wide×0.060 inch (1.5 mm) deep and merge into two channelseach about 0.500 inch (12.7 mm) wide×0.060 inch (1.5 mm) deep. Thebranch channels are of equal length and cross-section so as to producesubstantially equal pressure conditions during use. Cavity 27 is alsoemployed in the generation of reciprocatory pulsations as describedbelow. From cavity 27, the plasma-depleted blood is conducted throughshallow channel 28, 0.200 inch (5.1 mm) wide×0.060 inch (1.5 mm) deep,and through module plasma-depleted blood outlet 29 which extends throughmatched ports in plates 32, 19B, i.e., cavity 27 is between blood flowpaths outlets 25 and module plasma-depleted blood outlet 29.

Plasma which passes through the membranes flows radially in a plasmaflow path, e.g., on the membrane which lies between end plate 19A andadjacent plate 32, the plasma flow path is between the membrane andplate 32. The plasma flow path is comprised of radial flow channelswhich culminate in a perimeter plasma collection channel, as illustratedby FIG. 3, from which the plasma passes through matched ports 33 inplates 32, 19B and out of the module. A section of plasma flow channelsare also illustrated in FIG. 1.

The entire module is enclosed by envelope 30, which is cut away forpurposes of illustration. It is comprised of two sheets of a flexibleblood-impermeable material, such as poly(vinyl chloride), the sheetsbeing joined together at seal 31 around the perimeter of the stack. Theenvelope thus provides a unitary flexible enclosure for the module whichretains the plates and membranes in proper relationship. The threeapertures 20, 29, 33 in end plate 19B mate with tube connections inenvelope 30 as illustrated in FIG. 5.

Envelope 30 covers and seals the various channels, cavities andapertures in end plate 19A and forms a flexible diaphragm over eachcavity 22, 27. A perimeter lip, not shown, around each cavity andchannel in end plate 19A aids in sealing. Reciprocatory pulsations aregenerated by alternately compressing the diaphragm over each of cavities22, 27. Reciprocating plungers which are useful for this purpose areillustrated by FIG. 7.

FIG. 2 illustrates a blood side support comprised of plate 32, a surfaceof which is provided with recessed radial blood flow channels 24.Between channels 34 are ridges 36. The channels 34 extend fromcounterbore 37 around inlet 24. For purposes of illustration, only aportion of enlarged blood flow channels are shown. In fact, ninetychannels 34 extend around the entire perimeter of inlet 24 although moreor fewer channels may be employed. The channels 34 are at least about 4mils (0.1 mm) deep, preferably about 4 to 10 mils (0.1 to 0.3 mm). Theyare narrow around the inlet and increase in width from about 8 mils (0.2mm) to about 250 mils (6.4 mm). The counterbore is about 20 mils (0.5mm) deep and 0.5 inch (12.7 mm) in diameter. Around the perimeter offlow channels 34 is perimeter plasma-depleted blood collection channel35 which leads to plasma-depleted blood outlet ports 25. Between flowchannels 34 and collection channel 35 are blood pressure balancing andsealing grooves comprising a perimeter border of short narrow channels34', each about 4 to 30 mils (0.1 to 0.8 mm) wide. Between perimeterchannels 34' are ridges 36'. Perimeter channels 34' enhance uniformdistribution of pressure and flow within the blood flow channels bycausing increased velocity and hence increased pressure drop across theperimeter channels.

In region 38, the channels are spaced inward from the edge of the plateso as to avoid intersecting any of ports 20, 33, 29. The channels 34 areoffset from radial plasma flow channels on a plasma side support so thatthe ridges between the blood flow channels and the ridges between theplasma flow channels will not be contiguous but rather will intersect,thus minimizing the risk of membrane shearing; in the illustratedembodiment, approximately the outer 80% of the axes of flow channels 34are angled slightly from a pure radial direction. Also to minimize therisk of shearing, the ridges between the channels preferably have flatsurfaces, e.g., about 3 to 10 mils (0.1 to 0.3 mm) wide.

Alignment pins 39 and 40 fit snugly into aligned holes in each plate19A, 19B, 32 thus maintaining the plates in the proper relativeorientation.

The preferred plasma side support, opposite the blood side support, isillustrated by FIG. 3. The plasma side support comprises the othersurface of plate 32, having plasma flow channels 41 recessed in onesurface thereof with ridges 42 therebetween. The plasma flow channels 41extend from an inlet sealing surface 43 in zones of progressivelygreater numbers to a perimeter plasma collection channel 44, which isabout 0.07 inch (1.8 mm) wide×0.030 inch (0.8 mm) deep. For purposes ofillustration, only a section of enlarged plasma flow channels are shownin the Figure. By progressively increasing the numbers of plasma flowchannels, closely-spaced ridges, which provide support for the membrane,are maintained. In the illustrated plasma side support, the number ofplasma flow channels doubles in each succeeding zone so that in theinnermost zone there are 90 such channels and in the outermost zonethere are 1440 such channels.

In the center of plate 32 is blood flow path inlet 24, e.g., about 0.39inch (9.9 mm) in diameter, which is in registry with blood flow pathinlet 24 in plate 19A.

Inlet sealing surface 43 is an area on the plasma side support which iscoplanar with the nonrecessed areas of the support. It is oppositenarrow blood flow channels on an opposing blood side support so thatwhen the supports are pressed together with a membrane therebetween,blood is substantially prevented from leaking into plasma flow regionswithout the use of adhesives or gaskets. Surface 43 is a circular area,concentric with inlet 24 and of larger diameter, e.g., about 1 inch(25.4 mm). Preferably, it is an inlet sealing boss although otherelements can be used, e.g., an annular insert. It substantially preventsblood from leaking from inlet 24 to plasma flow channels 41. The plasmacollection channel 44 is located within a smaller radius than the short,narrow channels 34'on plate 19A. Between the plasma collection channel44 and the edge of plate 32 is a perimeter sealing surface 45 which canbe pressed against channels 34', there being a membrane therebetween,effecting a seal in a manner similar to the seal around inlet 24.

From the plasma collection channel 44, plasma flows to plasma outlet 33.As with the blood side support, the channels are spaced inward from theedge of the plate in region 46.

The interior surface of plate 19A in FIG. 1 also comprises a blood sidesupport identical to that shown in FIG. 2. Several plates 32 can bestacked to permit use of a desired number of membranes, the preferrednumber being four to six. The last plate, i.e., end plate 19B, comprisesa plasma side support, on its interior surface, which is identical tothe plasma side support illustrated in FIG. 3 except that end plate 19Bis not apertured with blood flow path inlet 24. On its exterior surface,end plate 19B is plain.

FIG. 4 illustrates the central sealing design of the module and thepreferred blood flow path entrance design. The membrane 47 is pressedbetween the blood side support surface of one plate 32A and the plasmaside support surface of a second plate 32B. In this figure, thee is nocounterbore around the inlet on the blood side support as there is inFIG. 2. Membrane 97 bridges the narrow blood flow channels around inlet24 and is squeezed against central sealing boss 43 of the next plate,acting in this region as seal members in a manner similar to a checkvalve. By employing channels which are about 4 to 20 mils (0.1 to 0.5mm), preferably 6 to 10 mils (0.2 to 0.3 mm), in width, under usualoperating conditions, i.e., pressures up to about 3 psi (21 kPa), themembrane seal has been found to substantially prevent leakage of bloodeven when reciprocatory pulsatility is employed, when the module ispressed between clamp jaws.

As can be seen in FIG. 4, the entrance to each blood flow channel isinitially deep but uniformly decreases in depth, as the flow channelswiden, such that the cross-sectional area of each is substantiallymaintained while the depth is decreased. This design enhances uniformflow in the module and allows the flow conditions in the thin channelsto be attained more gradually than if the entrances to the channels werealso thin. The initial depth is greater than about 10 mils (0.3 mm),preferably about 15 to 20 mils (0.4 to 0.5 mm) and is graduallydecreased to about 4 to 10 mils (0.1 to 0.3 mm).

Envelope 30 allows the module to be purged of air and filled with aliquid, e.g., saline, prior to use. When the module is used, this salinesolution is swept out of the flow channels by blood and plasma butremains around the periphery of envelope 30 in the region of seal 31.Any blood which may leak into this solution in this region remains thereby a check-valve action, due to the seal between perimeter channels 34'and the perimeter sealing boss 45, illustrated in FIGS. 2 and 3, similarto that described for the sealing region surrounding inlet 24 in FIG. 4.

As shown in FIG. 5, tube 48 connections to the apertures 20, 33, 29 aremade by joining flanged plastic fittings 49 to the plastic envelope 30on the bottom of the unit as seen in FIG. 1. No direct connection ismade to any of the plates 19B, 19A, 32; however, the fittings are urgedagainst the envelope 30 and into shallow counterbores 50 in end plate19B by means of a clamping mechanism, namely, jaws 51, 52. Counterbores50 prevent the plates from moving relative to the envelope during use.Jaws 51, 52, faced with elastomer 53, 53', engage envelope 30 at the topof plate 19A and the bottom of plate 19B and, in addition to holding thetube fittings, urge the stacked plates together in leak-tight conditionresisting the hydrostatic pressure of the blood being pumped through themodule. Unit pressures within the module are in the order of 0.5 to 3psi (3.5 to 20.7 kPa) on an area of 40 sq. in. (250 sq.mm) resulting inclamp loadings of up to about 120 lb. (54.4×10.sup. 3 gm). The clampmust provide sufficient external pressure to offset this internalpressure as well as to compensate for compliance and manufacturingtolerances. This external pressure should be evenly distributed.

Referring to FIG. 6, jaw 52 is a rectangular platen having yoke 54bolted thereto. Yoke 54 has four legs, two shown; the number of legs isnot critical. Jaw 51 is a floating and self-aligning circular platen oflarger diameter than module 55 which is pressed against module 55 bymeans of central gear-reduced screw 56 extending through yoke 54 andconnected to jaw 51 by means of a swivel joint, not shown. A gearreducing mechanism, not shown, is fitted to the top of yoke 54. Twobosses 57, shown cut off, are on either side of screw 56 and housereciprocating plungers, as further described below with reference toFIG. 7. Elastomer 53, 53' lie between jaws 51, 52 and module 55. A guidepin, not shown, extending through yoke 54 to jaw 51 is used to properlyalign jaw 51 with module 55 upon clamping. It has been found that use ofsuch a clamping mechanism provides nearly uniform pressure across themodule and provides structural support external to the module, therebylowering the cost of the module which is a disposable unit.

FIG. 7 illustrates the reciprocating plungers of a pulse generatorintegral with jaw 51. It is a cross section taken perpendicular to thecross section of FIG. 6. Jaw 51 has bosses 57 for two parallel boresoccupied by plungers 58 which are shouldered to carry springs 59 whichurge the plungers toward reciprocatory pulse cavities. The plungers arelifted 180° out of phase with each other by means of eccentrics 60 on acommon shaft 61 which is carried in bearings, not shown, and is extendedoutside the bar for a belt connection to a motor drive, not shown, whichis mounted on brackets, not shown, extending from jaw 51. The eccentrics60 each engage a roller 62 in a slot in each plunger 58. Each roller 62is carried on a wrist pin in the plungers. The throw of the eccentricsis about 0.030 inch (0.8 mm) producing a plunger stroke of about 0.060inch (1.6 mm). The eccentric shaft drives the pistons down away from thediaphragm compressing the springs and storing energy. The pistons arereturned by the springs which limit the maximum force and resultingpressure which can be generated by the piston on the diaphragm over eachcavity. This also limits jamming damage should the unit be installedmisaligned or with a foreign body in the clamp cavity area. The plungersdisplace equal volumes forward and reverse.

The bottom of jaw 51 is pressed against plastic envelope 30 by the clampso that the plunger heads 58 enter reciprocatory pulse cavities.Rotation of shaft 61 caused diaphragm-like deflections in envelope 30and produces a pumping action on fluids in the cavities. This action isoscillatory, causing reciprocatory pulsatile flow on the surfaces of themembranes. Because the reciprocatory pulse cavities are integral withthe modular assembly of stacked plates and membranes, there is minimaladdition to the average hold-up time of the blood being processed andeach flow fraction receives uniform treatment.

FIGS. 8 and 9 illustrate, respectively, an alternative blood sidesupport and an alternative plasma side support which may be used in asecond illustrative embodiment of a module of the invention, such as themodule illustrated by FIG. 10. Referring to FIG. 8, at the center of theplate is blood flow channel inlet 63 surrounded by counterbore 64, whichis about 0.5 inch (12.7 mm) in diameter and about 20 mils (0.5 mm) indepth. From the counterbore, radial flow channels 65, shown enlarged andin part, are narrow around the inlet and extend to a perimeterplasma-depleted blood collection channel which is a series ofplasma-depleted blood collection channels 66, 67, 68. These channelslead to plasma-depleted blood outlet 69. In the illustration is shown afirst perimeter channel 66 which has four equidistant exits tointermediate channels 67 each of which in turn have an exit to finalchannel 68. Each channel is about 0.070 inch (1.8 mm) wide×0.030 inch(0.8 mm) deep. These channels comprise blood pressure balancing andsealing grooves serving in this regard, the same purpose as theperimeter border of short narrow channels 34' in FIG. 2. The channelsare spaced inward in region 70 to avoid plasma channels and ports.

FIG. 9 illustrates a plasma side support which may be used with thealternative blood side support of FIG. 8. It differs from the plasmaside support described above in FIG. 3 in the locations of blood outlet69 and plasma outlet 71, the latter of which is in a protrusion 72 fromthe edge of the plate in order to avoid the various blood flow channelsand ports. Sealing around the inlet is accomplished as illustrated abovein FIG. 4. Sealing around the perimeter is effected by acheck-valve-like action resulting from pressing a membrane betweenchannels 66, 67, 68 on the blood side support and perimeter sealingsurface 73 on the plasma side support, in a manner similar to, thoughnot as effective as, that described above with reference to FIGS. 3 and4.

A second illustrative embodiment of a module of the invention employingthe blood and plasma side supports of FIGS. 8 and 9 is shown in FIG. 10.This illustrative embodiment is not fitted with reciprocatory pulsecavities. Blood enters the module through blood flow path inlet 63,passes through blood flood flow channels, not shown, in blood sidesupports, not shown, and exits through plasma-depleted blood outlet 69.Plasma which passes through membranes between plasma and blood sidesupports flows radially to plasma collection channels and out of themodule via plasma outlet 71. An external clamping mechanism, such as themechanism described above absent the pulse generator, is used to providestructural support

Reciprocatory pulsations, according to the invention of a differentinventive entity, are generated by an oscillating peristaltic pump 73 ona loop 74 of flexible tubing extending between blood inlet 63 andplasma-depleted blood outlet 69.

BEST MODE

The best mode for carrying out the invention is illustrated by FIGS. 1through 7 and the descriptions thereof.

While the preferred embodiments of the invention are illustrated anddescribed above, it is to be understood that the invention is notlimited to the precise constructions herein disclosed and that the rightto all changes and modifications coming within the scope of thefollowing claims is reserved.

We claim:
 1. Plasmapheresis filtration module comprising a plasma sidesupport having a blood inlet sealing surface, a blood side supporthaving a multiplicity of blood flow channels around the periphery of ablood inlet, and a planar membrane pressed between the plasma sidesupport and the blood side support, the blood flow channels beingopposite the inlet sealing surface so that blood flows on the bloodside, but not on the plasma side, of the membrane, said module beingcircular and having a central inlet with a generally radial blood flowpath extending therefrom between the blood side support and themembrane, wherein said module the plasma side support has generallyradial plasma flow channels extending from the inlet sealing surface toa plasma collection channel and the blood flow channels extend radiallyfrom the inlet to a plasma-depleted blood collection channel, andwherein said module the entrances to the blood flow channels uniformlydecrease in depth from greater than about 15 mils (0.4 mm) to about 4 to15 mils (0.1 to 0.4 mm) and the initial width of the entrances is about4 to 20 mils (0.1 to 0.5 mm).
 2. Module of claim 1 in which the plasmaand blood flow channels are offset.
 3. Module of claim 1 in which theplasma flow channels extend in zones of progressively greater numbers.4. Module of claim 3 in which the entrances to the blood flow channelsuniformly decrease in depth from about 15 to 20 mils (0.4 to 0.5 mm) toabout 4 to 10 mils (0.1 to 0.3 mm), the initial width of the entrance isabout 4 to 20 mils (0.1 to 0.5 mm) and the cross-sectional area of theentrances remains substantially constant as the channels decrease indepth.
 5. Module of claim 3 in which the blood side support has a seriesof plasma-depleted blood collection channels.
 6. Module of claim 3 inwhich the plasma and blood flow channels are offset.
 7. Module of claim3 in which the blood side support has a perimeter border of channels toenhance uniform distribution of pressure and flow within the blood flowchannels, and the plasma side support has a peripheral sealing surface.8. Module of claim 7 in which the plasma and blood flow channels areoffset.
 9. Module of claim 8 which comprises a sealing envelope. 10.Module of claim 9 which comprises a polycarbonate or polyester membranehaving 0.1 to 1.0 μm pores.
 11. Module of claim 9 which comprises aplurality of membranes interleaved between a stack of plates including afirst and second end plate and an intermediate plate, the first endplate being a blood side support on its interior surface, the second endplate being a plasma side support on its interior surface and eachintermediate plate being a blood side and a plasma side support onopposite surfaces.
 12. Module of claim 11 which has tube connections tomodule inlet, plasma outlet and module plasma-depleted blood outletapertures, mated to the sealing envelope.
 13. Module of claim 12 whichis purged of air and filled with liquid.
 14. Module of claim 12 pressedbetween clamp jaws.
 15. Module of claim 12 or 13 in which there are fourto six membranes; the plates are about eight inches in diameter; and,the tube connections are flanged plastic fittings joined to theenvelope, which fittings are urged against the envelope and intocounterbores around the apertures, all of which are located in one ofthe end plates, by clamp jaws.